Pyruvate Dehydrogenase Complex: Pyruvate to Acetyl-CoA

The pyruvate dehydrogenase complex (PDC) links glycolysis to the citric acid cycle. It runs in the mitochondrial matrix and converts pyruvate (3 carbons) to acetyl-CoA (2 carbons).

Net reaction

Pyruvate + CoA + NAD⁺ gives acetyl-CoA + CO₂ + NADH.

Per pyruvate: one CO₂ lost, one NADH made. Per glucose (two pyruvate): 2 CO₂, 2 NADH, 2 acetyl-CoA.

Cofactors

Five are used: thiamine pyrophosphate (B1), lipoic acid, CoA (B5, pantothenate), FAD (B2) and NAD⁺ (B3). A shortage of B1 stalls the complex, so pyruvate and lactate build up.

Regulation

Products inhibit the complex, which makes sense: plenty of acetyl-CoA and NADH means the cell has fuel and reducing power.

Irreversible

The reaction has a large negative delta G, and animals cannot make glucose from acetyl-CoA. Fatty acids, which break down to acetyl-CoA, therefore cannot become net glucose.

Arsenic and PDC

Arsenic binds lipoic acid and inhibits the complex. Expect a clinical vignette that links it to high blood pyruvate.

Common traps

• Counting CO₂ per glucose as one. It is two, because there are two pyruvate.
• Placing PDC in the cytosol. It is in the matrix.
• Saying ATP is made directly. PDC makes NADH, which pays off later in the electron transport chain.

One-minute recap

• Pyruvate to acetyl-CoA, CO₂ and NADH, in the matrix.
• Five cofactors; B1 deficiency stalls it.
• Inhibited by acetyl-CoA, NADH and ATP; irreversible.